Gram-negative bacteria are at the root of about 30% of the hospital-acquired infections in the U.S., researchers said.

Action Points

Explain to interested patients that drug resistance among bacteria is a growing issue, that Gram-negative bacteria have several ways of developing resistance, and that such pathogens play a major role in some hospital-acquired infections.

Gram-negative bacteria are at the root of about 30% of the hospital-acquired infections in the U.S., researchers said.

Although they don't account for the majority of these types of infections, they have "features that are of particular concern," including highly efficient ways of gearing up for drug resistance and a host of resistance mechanisms, according to Anton Peleg, MD, and David Hooper, MD, both of Massachusetts General Hospital in Boston.

Those elements, combined with the absence of new drug development, have created a "perfect storm" around the Gram-negative pathogens, they said in a review article in the May 13 issue of the New England Journal of Medicine.

Gram-negative bacteria are the predominant players in ventilator-associated pneumonia and urinary tract infections -- 47% and 45%, respectively -- and the rates are about 70% for both in intensive care units, they said.

Ventilator-associated pneumonia occurs in between 10% and 20% of patients on the machines for longer than 48 hours, Peleg and Hooper said. The condition is linked to significant increases in length of hospital stay, mortality, and costs.

There are also reports of organisms resistant to all available antibiotics, the researchers said.

And physicians need to be aware of a recent clinical entity: healthcare-associated pneumonia. These are community-acquired pneumonia cases in which the patient has direct or indirect contact with a healthcare or long-term care facility.

When such patients are subsequently admitted, they are more likely to have a coexisting illness and to get ineffective empirical therapy. Their risk of death is greater than that of patients with true community-acquired pneumonia, the researchers said.

"The diagnosis of ventilator-associated pneumonia remains challenging," the researchers said, and there is no "easily obtained reference standard." Along with clinical criteria, therapy should be guided by microbiologic assessment, they added.

The vast majority of urinary tract infections are associated with urethral catheterization, the researchers said, and the most effective management is simply to take out the catheter.

Here, Escherichia coli is the key player, followed by P. aeruginosa, klebsiella species, enterobacter species, and A. baumannii, they said.

Gram-negative bacteria also play an important role in bloodstream infections -- about 30% of cases in the ICU are caused by one or another species of klebsiella, E. coli, enterobacter species, and P. aeruginosa.

However, Peleg and Hooper said, "given an adequate portal of entry, almost any Gram-negative organism can cause bloodstream infection."

The most recent challenge facing doctors in these cases has been the spread of carbapenemase-producing Enterobacteriaceae, they said, which have now been identified in 20 states.

In both bloodstream infections and ventilator-associated pneumonia, speedy provision of appropriate antibiotics improves outcomes, the researchers said. Indeed, delay in such therapy is associated with excess mortality in cases of bloodstream infection.

Physicians should be aware of the local microbial ecology -- the types of resistant bacteria -- and keep it in mind when prescribing empirical therapy for pneumonia or bloodstream infections, Peleg and Hooper said.

"The importance of knowing local antimicrobial susceptibility to direct empirical antibiotic therapy cannot be overemphasized," they said.

There remains discussion about the value of drug combinations, but for empirical therapy evidence is mounting that combination therapy raises the odds that at least one active drug is being given, they said.

Again, however, the drugs used need to be tailored to the local environment, they said. "We recommend institution-tailored combination therapy for the empirical treatment of serious hospital-acquired Gram-negative infections, followed by de-escalation to monotherapy once susceptibilities have been determined."

The authors did not report external financial support for the article. Peleg reported financial links with Abbott Molecular and Ortho-McNeil-Janssen. Hooper reported links with Pfizer, Novexel, Cubist, Johnson & Johnson, Mutabilis, and Daiichi-Sankyo.

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